An Open-label, Sequential Non-randomised Pharmacokinetics Study of DTG Plasma Exposure When Given as Twice or Once Daily DTG in the Presence of Rifampicin in Children With HIV and TB Between 20-35kgs in SA
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (Ctrough) of DTG 50mg twice daily
研究概览
简要总结
Stage 1 proposed study will provide evidence to support the use of twice-daily dose 50mg DTG in children (20-35kgs) co-treated with RIF.
Note: An amendment has been added to include children from 3kgs and a dose of 10mg dispersible DTG
详细描述
This is a single centre, open-label, non-randomised, prospective study evaluating the steady-state pharmacokinetics of twice-daily dose DTG administered during concurrent RIF treatment and assessing safety and tolerance in HIV-TB co-infected children weighing 20 to 35 kg.
DTG will be administered as a twice-daily dose 50mg tablet formulation both before starting and after completion of the standard six-month RIF-based anti-TB treatment. The NRTI background and anti-TB drugs will be prescribed following the national weight band dosing guidelines.
Those initially diagnosed with TB are likely to be sicker, and the recommendation is to start anti-TB treatment first and follow with ART two weeks later.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 23 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children <18 years with confirmed HIV-1 infection weighing 20-35kg ART-naive or experienced, with plans to use DTG for HIV treatment
- •Diagnosis of TB disease with clinician initiating rifampicin-containing first-line therapy
- •Parents/legal guardians/caregivers and children give informed written consent (or assent, where applicable) to be in the study
- •Girls who have reached menses must have a negative pregnancy test at screening and be willing to adhere to two effective methods of contraception (barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment) if sexually active. The parents/caregivers will be counselled together with the child if the child tests positive in order to reduce any social harm which may arise.
排除标准
- •History or presence of known allergy or contraindications to DTG
- •Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN and bilirubin ≥2xULN
- •Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones)
- •Pregnancy or breastfeeding
- •A concurrent illness that could influence drug PK, i.e. severe diarrhoea, vomiting, renal or liver disease
- •Treatment with concomitant medications known to have interactions with DTG
- •Participants that are eligible for the study but refuse to give consent and/or assent
研究组 & 干预措施
Twice Daily DTG
Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment / Twice daily Dolutegravir (10mg) dispersible
干预措施: Dolutegravir 50 MG (Drug)
Twice Daily DTG
Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment / Twice daily Dolutegravir (10mg) dispersible
干预措施: Dolutegravir 10 MG (Drug)
结局指标
主要结局
Pharmacokinetics (Ctrough) of DTG 50mg twice daily
时间窗: 48 weeks
Description of the pharmacokinetics (Ctrough, Cmax and AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Pharmacokinetics (Cmax) of DTG 50mg twice daily
时间窗: 48 weeks
Description of the pharmacokinetics (Cmax) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Pharmacokinetics (AUC0-24h) of DTG 50mg twice daily
时间窗: 48 weeks
Description of the pharmacokinetics (AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
次要结局
- To develop an integrated model which will be used to estimate the primary PK parameters of DTG(48 weeks)
- Adverse events(48 weeks)
- Virological suppression(48 weeks)
- Enzyme polymorphisms(48 weeks)
研究者
Dr Moherndran Archary
Dr Moherndran Archary
University of KwaZulu